Results from both our laboratory and others indicate that macrocephaly is present in 14-26% of children and adults with idiopathic autism. MRl studies and post mortem studies of brain weight suggest that macrocephaly in autism is due to megalencephaly, abnormal enlargement of the brain. Results from our laboratory indicate that in autistic individuals unselected for head size, brain size is increased due to increased volume of the parietal, temporal and occipital (i.e., posterior) lobes. Relative to total brain volume the size of the corpus callosum is disproportionately decreased. Additional data suggest that cortical enlargement is predominantly right-sided. MR studies from other centers support the validity of these findings.- Neuropsychological and neurobiological evidence now suggest that autism is a disorder of a complex distributed neural network resulting in anomalous brain organization and connectivity. The finding of megalencephaly in autism suggests that abnormalities of cellular proliferation or programmed cell death are also involved. The overall goal of this application is to build on our previous work in structural imaging and genetics by exploring abnormalities in brain size and shape in autistic individuals with megalencephaly and by examining the significance of these abnormalities for the pathogenesis of this disorder. We propose to: 1) examine anomalous patterns of growth and organization in autistic individuals with megalencephaly as evidenced by abnormalities in the relationship between (a) anterior and posterior cortical brain volume, (b) cortical and corpus callosum size, (c) gray and white matter volume, and, (d) right- and left-sided cortical lobe volumes; 2) explore developmental mechanisms that may underlie brain enlargement in autism by examining the trajectory of changes in head circumference overtime; 3) examine heterogeneity in the syndrome of autism by exploring the relationship between brain size and shape abnormalities on MRI to clinical features associated with autism including behavioral and neuropsychological characteristics.